Gene-Environment Interaction and Human Malformations

EPA Grant Number: R828292
Title: Gene-Environment Interaction and Human Malformations
Investigators: Shaw, Gary M. , Carmichael, Suzan L. , Finnell, Richard H. , Lammer, Edward J. , Torfs, Claudine P.
Current Investigators: Shaw, Gary M. , Carmichael, Suzan L. , Finnell, Richard H. , Lammer, Edward J. , Loffredo, Christopher A. , Torfs, Claudine P.
Institution: California Birth Defects Monitoring Program
Current Institution: California Birth Defects Monitoring Program , Children’s Hospital Oakland Research Institute , Georgetown University , Public Health Institute , Texas A & M University
EPA Project Officer: Deener, Kacee
Project Period: July 1, 2000 through June 30, 2005 (Extended to September 30, 2006)
Project Amount: $3,373,557
RFA: Genetic Susceptibility & Variability of Human Malformations (1999) RFA Text |  Recipients Lists
Research Category: Health Effects , Health

Description:

Human genetic susceptibility to pharmaceutical, chemical, or dietary exposures during pregnancy represents the basis of many potentially causal associations for congenital malformations. Only recently have the methods to measure genetic susceptibility to environmental exposures in large populations become available. The goal of this research is to elucidate gene-environment interactions underlying etiologies of human malformations. This multi-disciplinary research program will investigate the hypotheses that genetic variation of candidate genes involved in impaired detoxification pathways, folate metabolism and transport, and vascular integrity modify risks of human malformations.

Approach:

Combining state-of-the-art genotyping methods with rigorously designed population-based epidemiologic data collection, the specific aims for this research program are: 1) to analyze if genetic variation of infant and maternal genes involved in biotransformation and detoxification modify risks of malformations, in the presence or absence of selected maternal exposures to toxicants; 2) to analyze if genetic variation of infant or maternal folate-pathway genes modify risks of malformations, in the presence of variations in maternal folate intakes; and 3) to analyze if genetic variation of infant genes associated with vascular development and function modify risks of malformations, in the presence or absence of maternal exposures to vasoactive chemicals. The case-control research design will include 5000 cases and controls and will focus on these malformations: neural tube defects, selected heart malformations, orofacial clefts, limb defects, gastroschisis, and intestinal atresias. The analytic plan will combine maternal interview data with multiplex polymerase chain reaction-based genotyping for nearly 40 candidate genes on over 7200 samples.

Expected Results:

This research will enhance scientific understanding of the relations among human genetic polymorphisms and developmental toxicity, which will undoubtedly have important implications for risk assessment and prevention of common, costly, and deadly congenital malformations.

Publications and Presentations:

Publications have been submitted on this project: View all 53 publications for this project

Journal Articles:

Journal Articles have been submitted on this project: View all 39 journal articles for this project

Supplemental Keywords:

RFA, Health, Scientific Discipline, Genetics, Health Risk Assessment, Epidemiology, Susceptibility/Sensitive Population/Genetic Susceptibility, Children's Health, genetic susceptability, Biology, health effects, risk assessment, sensitive populations, vulnerability, health risks, gene-environment interaction, exposure, human malformation, polymerase chain reaction, children, etiology, children's vulnerablity, toxicity, genotyping, biotransformation, dietary exposure, growth & development, pregnancy, developmental disorders, genetic susceptibility, maternal exposure, vascular development, environmental hazard exposures

Progress and Final Reports:

2001 Progress Report
2002 Progress Report
2003 Progress Report
2004 Progress Report
2005 Progress Report
Final Report